This research grant will examine the role of high dose methotrexate with calcium leukovorin rescue in the management of clinical colo-rectal cancer. The clinical studies will begin in patients with advanced measurable disease and, if efficacy is demonstrated, will progress towards adjuvant therapeutic trials. Therapy will range from initial doses of 50 mg/kg to a maximum dose of 250 mg/kg. Results will be related to a random allotment of patients with cachexia to a program of hyperalimentation to observe whether there are discernible effects on toxicity and response rates. Pharmacokinetic studies of MTX and the relationship of tumor levels of dihydrofolate reductase to antitumor response will also be evaluated.